宁波地区耐多药结核分枝杆菌喹诺酮耐药gyr基因突变研究

Quinolone resistance and gyr gene mutations in multi-drug resistant of Mycobacterium tuberculosis in Ningbo,China

目的为阐明宁波地区耐多药结核分枝杆菌(Multiple drug-resistant tuberculosis,MDR-TB)的gyr基因突变特征,深入研究MDR-TB对喹诺酮类药物耐药与gyr基因突变特征的关系。方法采用1%比例法对MDR-TB进行氧氟沙星药敏检测实验,通过DNA直接测序法分析MDR-TB的gyr基因突变情况。结果 120株MDR-TB临床分离株中有34株对喹诺酮耐药,总耐药率为28.33%(34/120)。34株耐喹诺酮菌株中,30株gyr基因发生突变,突变率为88.24%(30/34)。30株gyr基因发生突变的菌株中gyrA基因突变有29株,占96.67%(29/30),突变位点包括90、91和94位氨基酸;gyrB基因突变有2株,其中1株均合并gyrA基因突变,占6.67%(2/30),突变位点包括499和502位氨基酸。结论宁波地区MDRTB对喹诺酮类药物耐药形势较为严峻,gyrA基因突变与MDR-TB对喹诺酮类药物耐药相关。

To analyze the characteristics of gyr gene mutations in clinical isolates from the patients with multi-drug resistant tuberculosis （MDR-TB） and the relation between MDR-TB with quinolone resistance and gyr gene mutations, the susceptibility of the MDR-TB clinical isolates to quinolones was tested by the proportion method. The gyr gene mutations of MDR-TB strains were detected by PCR and the following direct DNA sequencing. Results showed that there were 34 strains with quin- olone resistance in 120 MDR-TB clinical isolates. The quinolones resistance rate was 28.33%. There were 30 with gyr mutations in 34 MDR-TB with quinolone resistance. Of 30 quinolone resistant MDR-TB with gyr mutations, 29 mutated at condon 90, 91 and 94 of gyrA gene. For 2 gyrB mutations, 1 was associated with gyrA gene mutations. The mutations sites of gyrB were at condon 499 and 502 of gyrB gene. This study shows that the situation of MDR-TB with quinolone resistance is very serious. The mechanism of quinolone resistance in MDR-TB is mainly in connection with the mutation of gyr gene.